SIRT1 Activation by Curcumin Pre-treatment Attenuates Mitochondrial Oxidative Damage Induced by Myocardial Ischemia Reperfusion Injury.

This study was designed to investigate the protective effect of Cur pre-treatment on myocardial IRI and to elucidate this potential mechanism. Isolated and in vivo rat hearts and cultured neonatal rat cardiomyocytes were subjected to IR. Prior to this procedure, the hearts or cardiomyocytes were exposed to Cur in the absence or presence of the SIRT1 inhibitor sirtinol or SIRT1 siRNA. Cur conferred a cardio-protective effect, as shown by improved post-ischemic cardiac function, decreased myocardial infarct size, decreased myocardial apoptotic index and several biochemical parameters, including the up-regulation of the anti-apoptotic protein Bcl2 and the down-regulation of the pro-apoptotic protein Bax. Sirtinol and SIRT1 siRNA each blocked the Cur-mediated cardioprotection by inhibiting SIRT1 signaling. Cur also resulted in a well-preserved mitochondrial redox potential, significantly elevated mitochondrial superoxide dismutase activity, and decreased formation of mitochondrial hydrogen peroxide and malondialdehyde. These observations indicated that the IR-induced mitochondrial oxidative damage was remarkably attenuated. However, this Cur-elevated mitochondrial function was reversed by sirtinol or SIRT1 siRNA treatment. In summary, our results demonstrate that Cur pre-treatment attenuates IRI by reducing IR-induced mitochondrial oxidative damage through the activation of SIRT1 signaling. PMID: 23880291 [PubMed - as supplied by publisher]
Source: Free Radical Biology and Medicine - Category: Biology Authors: Tags: Free Radic Biol Med Source Type: research